Morbid anatomy of 'erosive osteoarthritis' of the interphalangeal finger joints : an optimised scoring system to monitor disease progression in affected joints

Objectives To develop and validate a quantitative radiographic scoring system, the Ghent University Scoring System (GUSS), with better ability to detect progression over a shorter period of time in erosive osteoarthritis (OA) of the interphalangeal (IP) finger joints compared with the existing anatomic phase scoring system. Methods Thirty IP finger joints showing erosive features at baseline or follow-up were selected from 18 patients with erosive hand OA. Posteroanterior radiographs of these joints obtained at baseline, 6 and 12 months-totalling 90 images-were used for the study. All joints were first scored according to the original anatomic phase scoring system. Erosive progression and signs of repair or remodelling were then scored by indicating the proportion of normal subchondral bone, subchondral plate and joint space on an 11-point rating scale (range 0-100 with 10 unit increases). Inter-and intrareader reproducibility was studied using intraclass correlation coefficients (ICCs). Based on the within-variance of two readers, the smallest detectable change (SDC) was calculated and allowed identification of joints with changes above the SDC as 'progressors'. Results Longitudinal inter-reader ICC scores rated well for all variables and the total score (ICC 0.86-0.93). To identify 'real' change over background noise, a change of at least 40 units on the total score (range 0-300) over 12 months (SDC 0-12: 36.0), and 50 units over 6 months (SDC 0-6: 47.6) had to be present. 60% of the 30 joints were identified as 'progressors' over 6 months compared with 33.3% with the classical anatomical scoring system, and 70% versus 56.6%, respectively, over 12 months. Conclusion GUSS, is a reliable method to score radiographic change over time in erosive IP OA and detects more progression over a shorter period of time than the classical scoring system

Markers and outcome measures in chronic immune mediated artrhritis: from association studies to prediction models.

This work aims to illustrate how single biomarkers and standardized clinical measures can be used in the daily clinical practice rheumatologist’s decision making and how different markers and measures can be combined into prediction models and composite indices. The first part focuses on association studies. Three association studies of carriage of Crohn’s disease associated CARD15 polymorphisms are shown. We first investigated the association between carriage of CARD15 polymorphisms and SpA related symptoms in Crohn’s disease. Inversely, the association between gut inflammation in SpA and carriage of CARD15 polymorphisms was explored. Also, an association between carriage of CARD15 polymorphisms and anti-Saccharomyces cerevisiae antibodies in Crohn’s disease patients is demonstrated. The diagnostic properties of a test are explored into more detail in part 2, illustrated by the rheumatoid factor (RF) and anti-citrullinated protein/peptide antibodies (ACPA) determination in rheumatoid arthritis (RA). ACPA is a very specific test for RA, but the specificity of this test may differ between study populations. Combinations of ACPA, RF and HLA-shared epitope testing are explored by different (predicted) probabilities plots, based on logistic regression. They demonstrate that combined ACPA and continuous RF-testing is the most relevant combination. In part 3, different single clinical measures and composite indices to measure response to treatment in RA are evaluated. 511 RA patients treated with infliximab are investigated. After a loading regimen at week 0, 2, 6 and 14, the treating rheumatologist could decide to give a dose increase at week 22. This decision to give a dose increase can be considered as a measure of insufficient response and could be best modeled by the DAS28 at the moment of decision. The same patients were followed over 4 years and also DAS28, measured at week 14 or week 22, could best predict 4-year attrition to therapy. In the last part, different methods to construct prediction models are evaluated. Discriminant analysis and logistic regression may be less performing in real life datasets with missing values and high dimensionality. In such cases, computer intensive methods – such as support vector machines and multilayerd perceptrons - may be useful

Tumour necrosis factor blockade for the treatment of erosive osteoarthritis of the interphalangeal finger joints: a double blind, randomised trial on structure modification

Background Adalimumab blocks the action of tumor necrosis factor-alpha and reduces disease progression in rheumatoid arthritis and psoriatic arthritis. The effects of adalimumab in controlling progression of structural damage in erosive hand osteoarthritis (HOA) were assessed. Methods Sixty patients with erosive HOA on radiology received 40 mg adalimumab or placebo subcutaneously every two weeks during a 12-month randomized double-blind trial. Response was defined as the reduction in progression of structural damage according to the categorical anatomic phase scoring system. Furthermore, subchondral bone, bone plate erosion, and joint-space narrowing were scored according to the continuous Ghent University Score System (GUSS (TM)). Results The disease appeared to be active since 40.0% and 26,7% of patients out of the placebo and adalimumab group, respectively, showed at least one new interphalangeal (IP) joint that became erosive during the 12 months follow-up. These differences were not significant and the overall results showed no effect of adalimumab. Risk factors for progression were then identified and the presence of palpable soft tissue swelling at baseline was recognized as the strongest predictor for erosive progression. In this subpopulation at risk, statistically significant less erosive evolution on the radiological image (3.7%) was seen in the adalimumab treated group compared to the placebo group (14.5%) (P = 0.009). GUSSTM scoring confirmed a less rapid rate of mean increase in the erosion scores during the first 6 months of treatment in patients in adalimumab-treated patients. Conclusion Palpable soft tissue swelling in IP joints in patients with erosive HOA is a strong predictor for erosive progression. In these joints adalimumab significantly halted the progression of joint damage compared to placebo

Seven-year follow-up of infliximab therapy in rheumatoid arthritis patients with severe long-standing refractory disease: attrition rate and evolution of disease activity

This study is based on the results from a Belgian expanded access program in which patients with active refractory and erosive rheumatoid arthritis (RA) were treated with intravenous infusions of infliximab in combination with methotrexate. The objectives of this study were to evaluate the continuation rate of infliximab and its clinical effect over a 7-year period and to document the reasons for discontinuation

A nationwide survey on patient's versus physician's evaluation of biological therapy in rheumatoid arthritis in relation to disease activity and route of administration : the Be-Raise study

Objectives : Biological treatment of rheumatoid arthritis (RA) is one of the cornerstones of current treatment strategies for the disease. Surprisingly little information exists on whether the route of administration affects patients' treatment satisfaction. It is equally unclear whether rheumatologists are able to accurately perceive their patients' appreciation. Thus, the Belgian Beraise survey aimed to examine whether RA patient's experience of their current biological treatment coincided with the treating physician's perception. Methods : A nationwide cross-sectional survey was conducted by 67 Belgian rheumatologists providing data obtained from 550 RA patients. Patients under stable dose of biologics for at least 6 months, were enrolled consecutively and all completed questionnaires. Separate questionnaires were completed by the treating rheumatologist which evaluated their patient's perception of the route of treatment administration. This study therefore evaluates whether a treating physician perceives the satisfaction with the route of administration to the same degree as the patient. Results : Completed questionnaires were obtained from 293 and 257 patients who obtained treatment via the intravenous (IV) or subcutaneous (SC) route of administration, respectively. 58.4% of patients were in DAS28-CRP(3) remission. Patient satisfaction with disease control was higher (44% scored >= 9) than that of the treating physician (35%), regardless of the route of administration (p<0.01). No differences were seen for the patients treated with an IV as opposed to a SC route of administration. The physician's perception of patient's satisfaction with disease control was markedly lower for IV treated patients as opposed to SC treated patients (p<0.001). Conclusions : Patients' satisfaction with biological treatment is high, but there is a considerable mismatch between patients' and rheumatologists' appreciation on the route of administration of biological therapy in RA. Physicians consistently consider IV biological therapy to be less satisfactory. Patient's appreciation is largely dependent on disease control, irrespective of the route of administration. Therefore, and encouraging shared decision making, we suggest that physicians and patients discuss the route of administration of biologicals in an open way

Radiological sacroiliitis, a hallmark of spondylitis, is linked with CARD15 gene polymorphisms in patients with Crohn's disease

Background: Sacroiliitis is a common extraintestinal manifestation of Crohn's disease but its association with the HLA-B27 phenotype is less evident. Polymorphisms in the CARD15 gene have been linked to higher susceptibility for Crohn's disease. In particular, associations have been found with ileal and fibrostenosing disease, young age at onset of disease, and familial cases. Objectives: To investigate whether the presence of sacroiliitis in patients with Crohn's disease is linked to the carriage of CARD15 polymorphisms. Methods: 102 consecutive patients with Crohn's disease were clinically evaluated by a rheumatologist. Radiographs of the sacroiliac joints were taken and assessed blindly by two investigators. The RFLP-PCR technique was used to genotype all patients for three single nucleotide polymorphisms (SNP) in the CARD15 gene. Every SNP was verified by direct sequencing. The HLA-B27 phenotype was determined. Results: Radiological evidence of sacroiliitis with or without ankylosing spondylitis was found in 23 patients (23%), of whom only three were HLA-B27 positive. In contrast, 78% of patients with sacroiliitis carried a CARD15 variant v 48% of those without sacroiliitis (p = 0.01; odds ratio 3.8 (95% confidence interval, 1.3 to 11.5)). Multivariate analysis (logistic regression) showed that the association between sacroiliitis and CARD15 polymorphisms was independent of other CARD15 related phenotypes (ileal and fibrostenosing disease, young age at onset of disease, familial Crohn's disease) (p = 0.039). Conclusions: CARD15 variants were identified as genetic predictors of Crohn's disease related sacroiliitis. An association was demonstrated between these polymorphisms and an extraintestinal manifestation of Crohn's disease

Polymorphisms in the ficolin 1 gene (FCN1) are associated with susceptibility to the development of rheumatoid arthritis

Objectives. We investigated the possible association of rheumatoid arthritis (RA) with single nucleotide polymorphisms (SNP) within the ficolin (FCN) genes. Two SNPs in the FCN1 gene, four SNPs in the FCN2 gene and one SNP in the FCN3 gene were studied. Methods. The SNPs within the FCN genes were detected by an experimental INNO-LiPA methodology (Innogenetics, Belgium) in a population consisting of 338 RA patients and 595 controls. The significant SNPs were further evaluated in two subpopulations and related to carriage of the human leukocyte antigen-shared epitope (HLA-SE), rheumatoid factor (RF) and the presence of anti-citrullinated protein/peptide antibodies (ACPA). Results. Two SNPs in the FCN1 gene were significantly associated with RA: the A allele rs2989727 was significantly increased in RA patients (67%) compared with controls (60%) (P = 0.002). Also, the frequency of the G allele of rs1071583 was increased in RA patients (68%) compared with controls (61%) (P = 0.003). Analysis of agreement between SNPs suggested strong linkage between rs2989727 and rs1071583. Carriage of a FCN1 SNP was independent of carriage of the HLA-SE, RF status and ACPA positivity. Conclusions. We describe two linked SNPs in the FCN1 gene that are associated with the development of RA

Diagnostic value of anti-human citrullinated fibrinogen ELISA and comparison with four other anti-citrullinated protein assays

We studied the diagnostic performance of the anti-human citrullinated fibrinogen antibody (AhFibA) ELISA for rheumatoid arthritis (RA) in a consecutive cohort (population 1) and evaluated the agreement between the AhFibA ELISA and four other assays for anti-citrullinated protein/peptide antibodies (ACPAs) as well as rheumatoid factor in patients with longstanding RA (population 2). Population 1 consisted of 1024 patients with rheumatic symptoms; serum samples from these patients were sent to our laboratory for ACPA testing within the context of a diagnostic investigation for RA. Ninety-two of these patients were classified as having RA according to the American College of Rheumatology criteria and 463 were classified as non-RA patients. Population 2 consisted of 180 patients with longstanding RA and was used to assess agreement and correlations between five ACPA assays: anti-cyclic citrullinated peptide (CCP)1 and anti-CCP2 antibodies were detected using a commercially available ELISA, AhFibA using ELISA, and anti-PepA and anti-PepB antibodies using line immunoassay. Applying previously proposed cut-offs for AhFibA, we obtained a sensitivity of 60.9% and a specificity of 98.7% in population 1. Receiver operating characteristic curve analysis could not detect a significant difference in diagnostic performance between the AhFibA ELISA and anti-CCP2 assay. Performing a hierarchical nearest neighborhood cluster analysis of the five different ACPA assays in population 2, we identified two clusters: a cluster of anti-pepA, anti-pepB and anti-CCP1, and a cluster of AhFibA and anti-CCP2. In conclusion, we found that AhFibA and anti-CCP2 antibodies had similar diagnostic performance. However, disagreement between ACPA tests may occur